Efficacy of convective-diffusion models to study the transient behaviour of a sewage-sludge-filled packed column for aqueous phase adsorption of fluoroquinolones: Consideration of pseudo-kinetics driven depletion of species

Ciprofloxacin and ofloxacin belong to a class of antibiotics called Fluoroquinolones (FQs), which have a wide anti-bacterial activity against Gram-positive and Gram-negative bacteria. Since the recent Covid-19 pandemic witnessed a magnanimous rise in the use of antibiotics to prevent secondary bacterial infections, it led to vast production and use of such antibiotics. Ultimately the antibiotics get discharged into the municipal sewer pipes, thereby killing the useful microbial colony. In order to prevent environmental degradation a commercial scale-up of the adsorption of these antibiotics using raw sewage sludge is an absolute necessity. In this study, a continuous adsorption operation is conducted in a packed bed of semi-dried raw sewage sludge to remove the FQs from wastewater. Two transient convective-diffusion models are developed including pseudo-first and second-order kinetics driven depletion terms. The models are optimised using the data collected under various dynamic conditions in order to analyse the performance of the packed bed in terms of bed height, flow rate and initial concentration of the FQs. Damköhler numbers of the FQs are estimated to predict the breakthrough times of both the FQs. The ratios of Damköhler numbers of ciprofloxacin and ofloxacin do not change much with flow rate. In all the experiments, Das << 1 for both the FQs, indicating a faster diffusion process with respect to the rate of pseudo-reaction. Diffusion reaches an ‘equilibrium' well before the reaction achieves pseudo-chemical equilibrium. Ratios of the Damköhler numbers, meant to represent the first-order and second-order convective-diffusion models for ciprofloxacin to ofloxacin is < 1. © 2023 Elsevier Ltd

Molecular detection of plasmid-mediated quinolone resistance genes among clinical isolates of Klebsiella pneumoniae during Covid-19 pandemic

Plasmid-mediated quinolone resistance (PMQR) genes confer low resistance to Fluoroquinolones (FQs). This study aims to detect five PMQR genes among FQs-resistant Klebsiella pneumoniae isolated from various clinical specimens. Out of 120 K. pneumoniae isolates, 68 FQs-resistance K. pneumoniae were included in a molecular study. Standard microbiological tests were used for identification and antimicrobial susceptibility. For the detection of PMQR genes, conventional polymerase chain reaction was used. A molecular study revealed that (73.5%) of samples harbored PMQR genes, and among them, 58% were co-carriages of PMQR gene variants. Aac (6')-Ib-cr gene was predominant (47.1%) among samples, and qepA had the lowest percentage (11.8%), qnr genes were (32.4%) (29.4%) (20.6%) qnrS, qnrB, and qnrA respectively. Overall, high percentages of PMQR genes were detected, and almost all of samples were phenotypically resistant to ciprofloxacin. As well, there was a significant statistical relationship between phenotypically ESBL-producers and qnrB and qepA genes.Copyright © Abdulkareem MM et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Computational evidence based perspective on the plausible repositioning of fluoroquinolones for COVID-19 treatment.

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a serious global healthcare crisis, so there is an emergence of identifying efficacious therapeutic options. In a setting where there is an unavailability of definitive medication along with the constant eruption of vaccine-related controversies, the drug-repositioning approach seems to be an ideal step for the management of COVID-19 patients. Fluoroquinolones (FQs) are commonly prescribed antibiotics for the treatment of genitourinary tract and upper respiratory tract infections, including severe community-acquired pneumonia. Research over the years has postulated multifaceted implications of FQs in various pathological conditions. Previously, it has been reported that few, but not all FQs, possess strong antiviral activity with an unknown mechanism of action. Herein, an interesting perspective is discussed on repositioning possibilities of FQs for the SARS-CoV-2 infections based on the recent in silico evidential support. Noteworthy, FQs possess immunomodulatory and bactericidal activity which could be valuable for patients dealing with COVID-19 related complications. Conclusively, the current perspective could pave the way to initiate pre-clinical testing of FQs against several strains of SARS-CoV-2.

Oral ß-lactams vs fluoroquinolones and trimethoprim/sulfamethoxazole for step-down therapy for Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae bacteremia.

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To compare rates of treatment failure for patients with bloodstream infections (BSIs) due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis who received oral step-down antibiotic therapy with either a fluoroquinolone (FQ) or trimethoprim/sulfamethoxazole (SXT) to rates for those who received an oral ß-lactam (BL). METHODS: This retrospective, multicenter, cohort study included 397 unique adult hospitalized patients with a BSI due to E. coli, K. pneumoniae, or P. mirabilis at 6 hospitals in central Texas between July 11, 2016, and July 11, 2018. The primary outcome was a composite of treatment failure comprising 30-day readmission due to recurrence, 30-day all-cause mortality, and change in oral antibiotic. Secondary outcomes included 90-day development of Clostridioides difficile infection, 90-day colonization with a multidrug-resistant organism, 90-day all-cause readmission, hospital length of stay, and the individual components of the primary outcome. RESULTS: Of the 397 patients included, 200 received oral step-down therapy with a BL while 197 received an FQ or SXT. Most patients had an infection due to E. coli (82.8%) and a urinary source of infection (85%). Median total duration of therapy was 14 days in both groups. No difference in treatment failure was identified between the groups treated with a BL and FQ/SXT (7% vs 5.8%, P = 0.561). Median hospital length of stay was the only secondary endpoint in which there was an observed difference (6 vs 5 days, P = 0.04). CONCLUSION: We observed no difference in treatment failure rates for patients receiving an oral BL compared to an oral FQ or SXT for step-down therapy of BSIs due to E. coli, K. pneumoniae, and P. mirabilis.

The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

Among all modern antibiotics, fluoroquinolones are well known for their broad spectrums of activity and efficiency toward microorganisms and viruses. However, antibiotic resistance is still a problem, which has encouraged medicinal chemists to modify the initial structures in order to combat resistant strains. Our current work is aimed at synthesizing novel hybrid derivatives of ciprofloxacin and norfloxacin and applying docking studies and biological activity evaluations in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole-substituted ciprofloxacin and norfloxacin derivatives. The structure and purity of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, UV-, IR- spectroscopy. Docking studies, together with in vitro research against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 27853, Candida albicans NCTC 885-653 revealed compounds in which activity exceeded the initial molecules.

Physiological response of Simocephalus vetulus to five antibiotics and their mixture under 48-h acute exposure.

Antibiotics, widely known as major environmental xenobiotics, are increasingly being released into ecosystems due to their essential functions in human health and production. During the COVID-19 pandemic waves, antibiotic use increases remarkably in treating bacterial coinfections. Antibiotics were initially expected only to affect prokaryotes, but recent research has shown that they can disturb the biological systems of eukaryotes, especially vulnerable aquatic creatures, through both direct and indirect processes. However, their toxicity to the freshwater cladoceran Simocephalus vetulus, an essential link in the aquatic food web, has never been evaluated. The effects of four fluoroquinolones (ciprofloxacin: CFX, ofloxacin: OFX, gatifloxacin: GFX, delafloxacin: DFX), tetracycline (TET), and a mixture of these medicines (MIX) on S. vetulus thoracic limb rate (TLR) were examined in this study. After S. vetulus was exposed to 20 and 40 mg GFX L-1, 90% and 100% mortality rates were recorded. At 2.5-10 mg L-1, GFX dramatically lowered the TLR of S. vetulus, resulting in a median effective concentration of 9.69 mg L-1. TLRs increased when the organisms were exposed to 10-40 mg L-1 of CFX and 1.25-40 mg L-1 of OFX. However, DFX and TET exposures did not affect TLRs. Exposure to MIX reduced TLR only at 40 mg L-1, suggesting an antagonistic interaction among the five pharmaceuticals. This study demonstrated that S. vetulus physiological responses to antibiotics, even in the same class, are complex and elusive. Beyond a common additive concentration principle, the antagonistic interaction of antibiotic mixture indicates a high level of uncertainty in terms of ecological dangers. We initially introduce S. vetulus to ecotoxicological studies of antibiotics, presenting the species as a low-cost model for physiological investigations of environmental xenobiotics.

[Oral antibiotic treatment of exacerbation of COPD. Beyond COVID-19]. / Tratamiento antibiótico oral de la exacerbación de la EPOC. Más allá de la COVID-19.

COPD (chronic obstructive pulmonary disease) includes patients with chronic bronchitis and / or emphysema who have in common the presence of a chronic and progressive airflow obstruction, with symptoms of dyspnea and whose natural history is modified by acute episodes of exacerbations. Exacerbation (EACOPD) is defined as an acute episode of clinical instability characterized by a sustained worsening of respiratory symptoms. It is necessary to distinguish a new EACOPD from a previous treatment failure or a relapse. EACOPD become more frequent and intense over time, deteriorating lung function and quality of life. The diagnosis of EACOPD consists of 3 essential steps: a) differential diagnosis; b) establish the severity, and c) identify its etiology. The main cause of exacerbations is infection, both bacterial and viral. Antibiotics are especially indicated in severe EACOPD and the presence of purulent sputum. Beta-lactams (amoxicillin-clavulanate and cefditoren) and fluoroquinolones (levofloxacin) are the most widely used antimicrobials. This review updates the problem of acute exacerbation with infectious origin from the perspective of etiology, antimicrobial resistance, microbiological studies, risk stratification, and antimicrobial management. The risk, prognosis and characteristics of COPD patients who develop COVID19 are analyzed.

[Safety in the selection of oral antibiotic treatment in community infections, beyond COVID-19]. / Seguridad en la selección del tratamiento antibiótico oral en las infecciones comunitarias, más allá de la COVID-19.

Oral antibiotics are among the most frequently used medications in the community. Its adverse effects are generally considered to be infrequent and mild, and include allergies, toxicities and drug interactions. Antibiotics are able to harm patients by various mechanisms, not always well known. Knowledge of the clinically relevant antibiotic-associated adverse effects can allow a judicious use based on the principle first do no harm, primun non nocere. In this review we explore the main adverse effects of oral antibiotics with specific focus on ß-lactams, macrolides, and fluoroquinolones.

In vitro inhibition and molecular docking of a new ciprofloxacin-chalcone against SARS-CoV-2 main protease.

BACKGROUND/AIM: SARS-CoV-2 is one of the coronavirus families that emerged at the end of 2019. It infected the respiratory system and caused a pandemic worldwide. Fluoroquinolones (FQs) have been safely used as antibacterial agents for decades. The antiviral activity of FQs was observed. Moreover, substitution on the C-7 position of ciprofloxacin enhanced its antiviral activity. Therefore, this study aims to investigate the antiviral activity of 7-(4-(N-substituted-carbamoyl-methyl)piperazin-1yl)-chalcone in comparison with ciprofloxacin against SARS-CoV-2 main protease (Mpro ). MATERIALS AND METHODS: Vero cells were infected with SARS-CoV-2. After treatment with ciprofloxacin and the chalcone at the concentrations of 1.6, 16, 160 nmol/L for 48 h, SARS-CoV-2 viral load was detected using real-time qPCR, SARS-CoV-2 infectivity was determined using plaque assay, and the main protease enzyme activity was detected using in vitro 3CL-protease inhibition assay. The activity of the chalcone was justified through molecular docking within SARS-CoV-2 Mpro , in comparison with ciprofloxacin. RESULTS: The new chalcone significantly inhibited viral load replication where the EC50 was 3.93 nmol/L, the plaque formation ability of the virus was inhibited to 86.8% ± 2.47. The chalcone exhibited a significant inhibitory effect against SARS-CoV-2 Mpro in vitro in a dose-dependent manner. The docking study into SARS-CoV-2 Mpro active site justified the importance of adding a substitution to the parent drug. Additionally, the assessment of the drug-likeness properties indicated that the chalcone might have acceptable ADMET properties. CONCLUSION: The new chalcone might be useful and has new insights for the inhibition of SARS-CoV-2 Mpro .

The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)-preliminary molecular docking analysis.

BACKGROUND: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified at the end of 2019. Despite growing understanding of SARS-CoV-2 in virology as well as many molecular studies, except remdesivir, no specific anti-SARS-CoV-2 drug has been officially approved. METHODS: In the present study molecular docking technique was applied to test binding affinity of ciprofloxacin and levofloxacin-two commercially available fluoroquinolones, to SARS-CoV-2 S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLPRO). Chloroquine and dexamethasone were used as reference positive controls. RESULTS: When analyzing the molecular docking data it was noticed that ciprofloxacin and levofloxacin possess lower binding energy with S protein as compared to the references. In the case of TMPRSS2 protein and PLPRO protease the best docked ligand was levofloxacin and in the case of E proteins and RNA-dependent RNA polymerase the best docked ligands were levofloxacin and dexamethasone. Moreover, a molecular dynamics study also reveals that ciprofloxacin and levofloxacin form a stable complex with E- and TMPRSS2 proteins, RNA polymerase and papain-like protease (PLPRO). CONCLUSIONS: The revealed data indicate that ciprofloxacin and levofloxacin could interact and potentially inhibit crucial SARS-CoV-2 proteins.

Fluoroquinolone Antibiotics Exhibit Low Antiviral Activity against SARS-CoV-2 and MERS-CoV.

Repurposing FDA-approved drugs that treat respiratory infections caused by coronaviruses, such as SARS-CoV-2 and MERS-CoV, could quickly provide much needed antiviral therapies. In the current study, the potency and cellular toxicity of four fluoroquinolones (enoxacin, ciprofloxacin, levofloxacin, and moxifloxacin) were assessed in Vero cells and A549 cells engineered to overexpress ACE2, the SARS-CoV-2 entry receptor. All four fluoroquinolones suppressed SARS-CoV-2 replication at high micromolar concentrations in both cell types, with enoxacin demonstrating the lowest effective concentration 50 value (EC50) of 126.4 µM in Vero cells. Enoxacin also suppressed the replication of MERS-CoV-2 in Vero cells at high micromolar concentrations. Cellular toxicity of levofloxacin was not found in either cell type. In Vero cells, minimal toxicity was observed following treatment with ≥37.5 µM enoxacin and 600 µM ciprofloxacin. Toxicity in both cell types was detected after moxifloxacin treatment of ≥300 µM. In summary, these results suggest that the ability of fluoroquinolones to suppress SARS-CoV-2 and MERS-CoV replication in cultured cells is limited.

Antimicrobial Management of Respiratory Infections in Severe Acute Respiratory Syndrome Coronavirus 2 Patients: Clinical and Antimicrobial Stewardship Programs Conundrums.

The role of empirical and even directed antimicrobial management of patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is problematic; antibiotics are used frequently among these patients to treat confirmed or suspected coinfection or just the symptoms. In the rapidly changing clinical landscape of SARS-CoV-2, there is minimal guidance for selecting appropriate treatment versus non-antimicrobial treatment, and clinicians are pressed to make daily decisions under the stress of absence of data while watching patients deteriorate. We review current data and patterns of antimicrobial use and the potential approach for antimicrobial stewardship in the context of SARS-CoV-2.